Studies on the genetics of viral leukemogenesis in wild mice have revealed that these mice differ substantially from the inbred strains. Analysis of a variety of feral mouse populations have shown that almost all lack ecotropic-MuLV related sequences. MuLVs with ecotropic host range have been isolated from M. hortulanus, M. m. castaneus and M. m. molossinus. Data from Southern blot hybridizations indicate that most of these viruses differ from ecotropic MuLVs of inbred mice in their hybridization properties and internal restriction maps. Cells of most wild mice also differ from inbred mice in their susceptibility to exogenous infection. Most lack the restriction defined by the known alleles at the Fv-1 locus. Genetic crosses demonstrated that 2 of these mice, M spretus and M. praetextus, carry the rare resistance allele at Fv-2. These mice also differ from laboratory mice in their susceptibility to xenotropic MuLVs. This trait is controlled by a single chromosome 1 locus, designated Sxv, which may represent a wild mouse polymorphism of the MCF-MuLV receptor locus.